1. Field of the Invention
The present invention relates to a novel CD33-like protein. In particular, isolated nucleic acid molecules are provided encoding the CD33-like protein. Recombinant CD33-like polypeptides are also provided as are recombinant vectors and host cells. The invention further provides methods useful during tumor or inflammatory disease diagnosis or prognosis and therapeutic treatments targeting cells expressing CD33-like polypeptides.
2. Background Information
CD33 was originally defined on human myeloid cells by a panel of monoclonal antibodies (MoAbs) that recognize a glycoprotein of 67 kD that is restricted in its expression to cells of the hematopoietic system (Peiper S. C. et al., in Knapp W, Dorken B, Gilks W R, Rieber E P, Schmidt R E, Stein H, von dem Borne A E G (eds): Leucocyte Typing IV. White Cell Differentiation Antigens. Oxford, UK, Oxford University 1989, p 814; Pierelli L. et al., Br J Haematol 84:24 (1993); Andrews R. G. et al., Blood 62:124, (1983); Griffin J. D., et al., Leuk Res 8:521 (1984)). CD33 is absent from hematopoietic stem cells but is first detected on a subpopulation of mixed colony-forming cells (Pierelli L. et al., Br J Haematol 84:24 (1993); Griffin J. D. et al., Leuk Res 8:521 (1984)). Expression then continues along the myelomonocytic pathway until it is downregulated on granulocytes but retained by monocytes and tissue macrophages. (Pierelli L. et al., Br J Haematol 84:24 (1993); Bernstein I. D. et al., J Clin Invest 79:1153 (1987)). The expression pattern of CD33 within the hematopoietic system indicates a potential role in the regulation of myeloid cell differentiation. However, despite its initial identification over 10 years ago (Andrews R. G. et al., Blood 62:124 (1983)), the functions and binding properties of CD33 have remained obscure.
CD33 MoAbs are of great importance in the immunodiagnosis of acute leukemias, allowing distinction between myeloid leukemic cells (acute myeloid leukemia (AML) French-American-British classification MI-7) and the usually CD33-negative cells of lymphoid origin. (Griffin J. D. et al., Leuk Res 8:521 (1984); Matutes E. et al., Haematol Oncol 3:179 (1985); Bain B. J.: Immunological cytogenetics and other markers, in Bain B J (ed): Leukaemia Diagnosis: A Guide to FAB Classification. London, UK, Gower Medical, 1990, p 61). This is especially valuable for the more immature forms of AML, where morphologic criteria are insufficient yet correct categorization is essential for prognostic predictions and the choice of therapy. CD33 MoAbs have also been used in preliminary therapeutic trials, principally for purging of the bone marrow of AML patients, either before transplantation or in case of diseases that are resistant to chemotherapy. (Robertson M. J. et al., Blood 79:2229 (1992); Applebaum F. R. et al., Transplantation 54:829 (1992); Caron P. C. et al., Cancer 73:1049 (1994)). Thus, due to the importance of CD33, there is a clear need to identify and isolate nucleic acid molecules encoding additional polypeptides having CD33-like protein activity.